Last month, Jorge Conde handed out the first of his company’s precious products: an engraved silver box housing a USB drive. On the drive, protected by encryption software, was the sequence of the recipient’s entire genome, a proprietary analysis of his genetic risks for disease, and software for browsing the data.
The event signals a shift in the world of human genome sequencing. Until now, the handful of people who have had their genomes sequenced, including genomics pioneers Craig Venter and James Watson, have been part of government or industry efforts to study the human genome or showcase new sequence technologies. But thanks to Knome, a startup based in Cambridge, MA, genome sequencing is no longer just a research tool. Anyone with $350,000 to spare and an adventurous spirit can now have his or her own genome sequenced.
Knome is at the forefront of the push toward so-called personalized medicine. Scientists and physicians hope that when sequencing costs come down enough, genetic analysis will become a ubiquitous part of health care, helping doctors choose the best treatments for a specific patient, or helping individuals take steps to prevent diseases for which they are at risk.
While Knome has not yet disclosed the number of people who have signed up for its service, it aims to sequence 20 genomes this year. “We have individuals at every stage of the process,” says Conde, Knome’s president and chief executive officer. “We collected data from additional clients in Europe last week and have people being sequenced now.” That number may grow as sequencing costs plummet: the company soon plans to announce a lower price. And competition from other companies, such as Illumina, based in San Diego, could push down costs further.
Cheaper personal-genomics services are already available: three companies–23andMe, Navigenics, and Decode–offer analysis of hundreds of thousands of genetic variations, to predict risk of disease or assess ancestry and other traits. But Knome sequences the entire genome–nearly all three billion bases. “That has a tremendous advantage, because the information is significantly greater and more complete than other services,” says Raju Kucherlapati, scientific director of the Harvard Partners Center for Genetics and Genomics at Harvard Medical School, in Boston. “Ultimately, this is the direction to go. The only impediment is really the cost.”
At this point, Knome’s customers are buying a product that has aspects of both a well-equipped Lamborghini and Internet service circa 1985. The $350,000 price tag is out of reach to all but a very few. But interpreting a person’s genome sequence requires comparing it with a database of human genetic information linking particular variations with health or other traits. The greater the number of genomes sequenced, the richer the analysis; but at the moment, that number is pretty low. “This information is going to be thorny and problematic in terms of interpretation,” says James Evans, a professor of genetics and medicine at the University of North Carolina at Chapel Hill and editor in chief of Genetics in Medicine. “We all have mutations and alterations that we simply don’t understand. As usual, the technology will be ahead of our ability to use it.”
Nonetheless, early adopters could give scientists insight into how to use the mammoth resource that is our genomic information. “They are trying to answer some of the more thorny questions about how this deluge of information will be used,” says Evans. “I believe it will give us some kind of idea of how to deal with this information when the price is more like $3,000.”
To provide a customer with personalized genome data, Knome extracts DNA from a blood sample and sends it to the Beijing Genomics Institute for sequencing. A team of informatics experts and medical consultants then analyzes the information, tailoring the process according to the interests of the client. “Each one is crafted to the individual,” says George Church, founder of the company and a geneticist at Harvard Medical School. (Church started the company to deal with the frequent requests that he fielded from wealthy people wanting to sequence their genomes.)
The first things the analysts look for are small variations that are found frequently in the broader population and have been linked to increased risk for myriad diseases. They then look for other types of genetic changes–including DNA deletions or duplications–linked to specific diseases. Lastly, they scan the genome for novel variations, changes that have not yet been spotted in the limited amount of human DNA that has been sequenced to date. The effects of such changes are uncertain, but the scientists try to predict them by considering the structure of the resulting proteins.
The results are revealed at a mini symposium dedicated to the recipient’s genome, where scientists explain the results, the process behind them, and their limitations. Knome’s first client, for example, found out that he was at increased risk for a particular disease that runs in his family. In this case, the finding didn’t affect his medical care–he was already being monitored for that condition by his physician. But Conde says that the company makes it clear that the information should not be viewed as a diagnostic or medical service. “If they choose to take medical action, they should only do so with the advice of a physician,” he says.
Clients can decide whether or not they want their data deposited in a public database accessible to genetic researchers. In what the research world might consider an ironic twist, Knome’s private service has generated a massive genomic resource: the company has likely accumulated the largest repository of whole-genome information in the world. Public projects to accumulate genome-wide databases, including the internationally funded 1,000 Genomes Project and Church’s Personal Genome Project, have focused early efforts on sequencing only the part of the genome that codes for proteins.